Abstract: ObjectiveTo explore the effects of celastrol on increasing embryonic development potential and fertility in
obese mice by improving the inflammatory state of granulosa cells. MethodsThe obese mouse model was established by
high-fat diet. qPCR method was used to detect the levels of inflammatory genes, apoptosis genes and hormone synthesis
genes in granulosa cells. The fertility was detected by mating experiment, and the improvement results were shown in the
comparison between the high-fat diet and the normal diet groups. Obese mice in the high-fat diet group were fed celastrol.
qPCR method was used to detect the expression of correlated genes in granulosa cells. The oocytes were fertilized by intracytoplasmic sperm injection method, and the embryonic development rate was calculated using the number of zygotes, 2-cell
embryos and blastocysts. The birth rate and other indicators were indicated by embryo transfer methods. ResultsCompared
with normal diet mice, the inflammatory genes Il-1β, Il-6 and apoptosis genes Bax, Bak1, Fadd, Traf2, Casp8 and Casp9
mRNA were significantly increased in granulosa cells in addition to the increased body weight, whereas hormone synthesis
genes Cyp11a1 and Cyp19a1 expression were significantly decreased in high-fat diet mice (P＜0.01). The embryonic
developmental rate, pregnancy rate and birth rate of obese mice also decreased significantly (P＜0.01). Compared with mice
in the high-fat diet group, the expressions of inflammation genes, apoptosis genes and hormone synthesis genes were
significantly improved in granulosa cells of celastrol group (P＜0.01), and there were no significant differences when
compared with the mice in the normal diet group (P＜0.01). The ovulation rate, embryonic development rate and birth rate
were significantly better in celastrol group than those in high-fat diet group (P＜0.01). Conclusion Celastrol can reduce
inflammatory gene expression in granulosa cells, relieve granulosa cell excessive apoptosis, restore granulosa cell hormone
secretion function, and therefore improve the fertility of obese mice.

Key words: tripterygium, granulosa cells, inflammation, genes, fertility, mice, obese, hormone synthesis, celastrol